Chen Shtaierman, Haim Bassan, Tali Peylan, Rachel Tsarfaty, Aviva Fattal-Valevski
Our objective in this paper is to study prospectively the additional risk that preterm infants born following ART have for developing ASD in comparison with naturally conceived preterm infants, based on the inconsistency between the studies available.
Preterm birth is emerging as a major public health problem in the whole developed world. Improvements in the management of preterm born neonates and their survival rates translate into increasing numbers of preterm survivors. Undoubtedly, one of the modern risk factors for prematurity is assisted reproductive technology (ART).
A body of research related to both short- and long-term outcomes among children conceived through ART has begun to emerge. Such research has raised questions concerning a range of health outcomes from conception to pregnancy and birth to long-term health and development. Many studies assessing neuro-cognitive outcomes (i.e. locomotor, cognitive, speech and language, behavior and autism spectrum disorder) in ART children showed no differences between ART-conceived and naturally conceived singletons, when adjusted for recognized confounding factors such as low birth-weight and prematurity.
Studies about the relationship of ART and autism spectrum disorders (ASDs) have shown inconsistent results.
According to the most recent report from the Centers for Disease Control and Prevention (CDC) for 2010, the overall prevalence of ASD among the ADDM sites in U.S.A. was 14.7 per 1,000 (1 in 68) children aged 8 years Israeli prevalence of ASD was calculated at 4.8 per 1,000 (1 in 208) for 1–12 years olds and 6.5 per 1,000 (1 in 154) for 8 year old children in 2010.
This study is a prospective follow-up of a cohort of 283 low birth prematurely born children between the years 1998 and 2002. All were admitted after birth to the Neonatal Intensive Care Unit (NICU) of the Lis Maternity Hospital at the Tel Aviv Medical Center in Israel (affiliated with the Tel Aviv University Sackler School of Medicine). We recruited 213 children; 46% males, mean gestational age 30.8±2.4 and mean birth weight 1,237±266 grams, 56% were product of multiple pregnancy. The mean age of the children was 12.8 years (range 11.1 to 14.4 years). We reviewed the medical charts of all the participants and gathered data on neonatal complications, developmental milestones and current behavioral diagnoses. The parents were requested to answer the A.S.S.Q. (Autism Spectrum Screening Questionnaire) that is accepted as a reliable screening tool for adolescents with social communication disorder related to the Autism Spectrum with high cognitive and adaptive functioning.
The incidence of ASD in the cohort was 24/213 (11.3%).
There was no difference between ASD and Non ASD diagnosed groups for the incidence of ART conception or any other risk factor at birth, with the exception of gender. We found 71% males in the ASD group compared with 43% males in the Non ASD group (p=0.015).
When compared the both groups for risk factors that were added after birth, during the NICU hospitalization, we found significant evidence of high incidence of apnea diagnosis (p=0.049), level of hyperbilirubinemia (p=0.001) and sepsis diagnosis (p=0.003). The review of the association between neuro-developmental diagnosis, revealed that there was a significant high incidence of co-morbidity between ADHD (p=0.085), Epilepsy (p=0.033) and Mental Retardation (=Intellectual Disability) (p=0.004) with ASD. We did not prove relevant association between ASD and CP or Learning Disorder.
In conclusion, the incidence of ASD in a cohort of preterm was found to be about ten times the general incidence reported in Israel to date.
The variables that differed significantly between the ASD group and non ASD diagnosed children were sepsis (p=0.003); apnea episodes (p=0.049) and hyperbilirubinemia (p=0.001).
The association between ASD and Male Gender, ADHD, Epilepsy and MR is well known and was also found in our cohort.
We found a 2.5 to 1 M/F ratio in our preterm cohort thus seems that the gender as risk factor is existent but less significant in prematurely born infants than in the general population (4 to 1).
ASD was not found to be associated with CP in our cohort.
ART was not proved to be a risk factor for the development of any neuro-developmental disorder.
Further studies with larger numbers of patients should be carried out to validate our results.